Exertional Exhaustion [PEM] Evaluated by the Effects of Exercise on [CSF] Metabolomics–Lipidomics and Serine Pathway in [ME/CFS], 2025, Baraniuk

The LP was 25-29 hours post the first of two identical exercise challenges, 24 hours apart.
Thanks.

Paper said:
Lumbar puncture was performed 1 to 5 h after [2nd] exercise.
So my opinion is that this sample most likely has been taken pre-PEM. The data generated could still be very valuable but I still think it would be better to acknowledge that it may well not represent the PEM state.

I believe that, with two-day stress tests, it would be ideal to test before, on the same day after the 1st test, on the same day after the 2nd test, and then on the day after the 2nd test. This could then potentially show when the PEM stage, if one can be seen, is detectable. I also get, in this particular example, how that many lumbar punctures would be undesirable for most people.
 
Because the timing of PEM is unpredictable, it actually would have been better (if the aim was to characterise CSF in PEM) to do the lumbar puncture when someone reported that they were experiencing PEM. (Although that would have been a nightmare for the participants.)

To evaluate PEM, cerebrospinal fluid metabolites and lipids were con- trasted in two independent cohorts of subjects who had lumbar puncture without exercise (non-exercise group) or after the second of two bouts of submaximal exercise performed on two consecutive days (post-exercise)

I think we have to get away from the idea that PEM reliably occurs at some magical number of hours after some formal exercise challenge. PEM is not the same as post-exertional effects. I'd like researchers to be more careful about how they describe their measurements. 'Post-exercise' is ok if the sample is taken after-exercise. But if they are trying to characterise PEM, then they need to sample at the time when the person with ME/CFS says they have PEM.

As I've mentioned before, I participated in a 2 day CPET with 48 hours between tests. I arrived tired from travelling, did the first CPET, and had PEM that night. The next day I was ok. And the next day I did the second CPET and felt okay. However, my CPET measures had dropped in what we consider a typical ME/CFS way. So, there was a physiological change, but I was not in what I would call 'PEM'.
 
I think we need a location to stay at for a few days if we’re going to get any answers about PEM. Or a team that travels around to collect samples at home at least once a day.

I’m hopeful that better biometric monitoring devices eventually will make it easier to know when you’re in PEM or not.
 
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